摘要
目的:探讨锌指蛋白(ZNF)772甲基化及高危型人乳头瘤病毒(HR-HPV)检测在意义不明的非典型鳞状细胞(ASCUS)病人分流中的意义.方法:选取初筛ASCUS病人195例,均接受HC2-HPV-DNA检测及ZNF772基因DNA甲基化检测;比较宫颈上皮内瘤样变(CIN) Ⅱ及以上与CIN Ⅱ以下、CIN Ⅲ及以上及CIN Ⅲ以下病人ZNF772基因位点甲基化水平的差异,并评估ZNF772甲基化水平及HR-HPV对ASCUS病人CIN Ⅱ及以上、CIN Ⅲ及以上的分流价值.结果:病理学检查显示,195例ASCUS病人中炎症80例(41.03％)、CIN Ⅰ64例(32.82％)、CIN Ⅱ29例(14.87％)、CIN Ⅲ/CIS/AIS 18例(9.23％)、SCC/AC 4例(2.05％).HR-HPV(HC2)阳性141例(72.31％)、HR-HPV(HC2)阴性54例(27.69％);CIN Ⅱ及以上病人HR-HPV(HC2)阳性检出率高于CIN Ⅱ以下(P<0.05);CIN Ⅲ及以上病人HR-HPV(HC2)阳性检出率高于CIN Ⅲ以下(P<0.05).CIN Ⅱ及以上、CIN Ⅲ及以上病人ZNF772基因-420、-422位点甲基化水平分别高于CIN Ⅱ以下、CIN Ⅲ以下病人(P<0.05).ZNF772基因-420、-422位点甲基化水平及HR-HPV诊断CIN Ⅱ及以上的AUC(95％CI)分别为0.867(0.811～0.911)、0.806(0.743～0.859)、0.777(0.712～0.834),诊断CIN Ⅲ及以上的AUC(95％CI)分别为0.891(0.838～0.931)、0.868(0.813～0.912)、0.780(0.716～0.836).ZNF772基因-420位点甲基化水平诊断CIN Ⅱ及以上、CIN Ⅲ及以上的AUC面积最大.结论:相较于HC2-HPV-DNA检测,ZNF772甲基化检测更能准确地识别ASCUS中CIN Ⅱ及以上、CIN Ⅲ及以上病变病人,有望成为分流ASCUS的有效替代手段.
Abstract
Objective:To explore the significance of zinc finger protein (ZNF) 772 methylation and high-risk human papillomavirus (HR-HPV) detection in the shunt of patients with atypical squamous cell of unknown significance (ASCUS) .Methods:A total of 195 initially screened ASCUS patients were selected,all of whom underwent HC2-HPV-DNA testing and ZNF772 gene DNA methylation testing.The differences in ZNF772 gene site methylation levels between patients with cervical intraepithelial neoplasia (CIN) Ⅱ and above and those with CIN Ⅱ and below,CIN Ⅲ and above and CIN Ⅲ and below were compared,and the ZNF772 methylation level and HR-HPV shunt value for ASCUS patients with CIN Ⅱ and above and CIN Ⅲ and above were evaluated.Results:Pathological examination showed that among 195 ASCUS patients,there were 80 cases of inflammation (41.03％),64 cases of CIN Ⅰ(32.82％),29 cases of CIN Ⅱ (14.87％),18 cases of CIN Ⅲ/CIS/AIS (9.23％),and 4 cases of SCC/AC (2.05％).One hundred and forty-one cases (72.31％) were positive for HR-HPV (HC2),and 54 cases (27.69％) were negative for HR-HPV (HC2);The positive detection rate of HR-HPV (HC2) in patients with CIN Ⅱ and above was higher than that in patients with CIN Ⅱ and below (P<0.05).The positive detection rate of HR-HPV (HC2) in patients with CIN Ⅲ and above is higher than that in patients with CIN Ⅲ and below (P<0.05).The methylation levels at the-420 and-422 loci of the ZNF772 gene in patients with CIN Ⅱ and above and CIN Ⅲ and above were higher than those in patients with CIN Ⅱ and below (P<0.05).The methylation levels at the-420 and-422 loci of the ZNF772 gene and the AUC (95％CI) for HR-HPV diagnosis of CIN Ⅱ and above were 0.867 (0.811-0.911),0.806 (0.743-0.859),and 0.777 (0.712-0.834),respectively.The AUC (95％CI) for diagnosis of CIN Ⅲ and above were 0.891 (0.838-0.931),0.868 (0.813-0.912),and 0.780 (0.716-0.836),respectively.The highest AUC area was detected for CIN Ⅱ and above,as well as CIN Ⅲ and above,based on the methylation level at the-420 locus of the ZNF772 gene.Conclusions:Compared with HC2-HPV-DNA detection,ZNF772 methylation detection can more accurately identify patients with CIN Ⅱ and above and CIN Ⅲ and above lesions in ASCUS,and is expected to become an effective alternative to shunt ASCUS.
维普
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